Regiodivergent Synthesis of 4- and 5-Sulfenyl Oxazoles from Alkynyl Thioethers.

The regiodivergent synthesis of 4- and 5-sulfenyl oxazoles from 1,4,2-dioxazoles and alkynyl thioethers has been achieved. Gold-catalysed conditions are used to favour the formation of 5-sulfenyl oxazoles via ß-selective attack of the nitrenoid relative to the sulfenyl group. In contrast, 4-sulfenyl oxazoles are formed by α-selective reaction under Brønsted acid conditions from the same substrates. The nature of stabilising gold-sulfur interactions have been investigated by natural bond orbital analysis, showing that the S→Au interactions are significantly stronger in the intermediate that favours the 5-sulfenyl oxazoles. A kinetic survey identifies catalyst inhibition processes. This study into the regiodivergent methods includes the development of telescoped annulation-oxidation protocols for regioselective access to oxazole sulfoxides and sulfones.

Interplay between α-synuclein and parkin genes: Insights of Parkinson's disease.

Parkinson's disease (PD) is a complex and debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The pathogenesis of PD is intimately linked to the roles of two key molecular players, α-synuclein (α-syn) and Parkin. Understanding the intricate interplay between α-syn and Parkin is essential for unravelling the molecular underpinnings of PD. Their roles in synaptic function and protein quality control underscore their significance in neuronal health. Dysregulation of these processes, as seen in PD, highlights the potential for targeted therapeutic strategies aimed at restoring normal protein homeostasis and mitigating neurodegeneration. Investigating the connections between α-syn, Parkin, and various pathological mechanisms provides insights into the complex web of factors contributing to PD pathogenesis and offers hope for the development of more effective treatments for this devastating neurological disorder. The present compilation provides an overview of their structures, regional and cellular locations, associations, physiological functions, and pathological roles in the context of PD.

Bioinspired Functionalization of Carbonyl Compounds Enabled by Metal Chelated Bifunctional Ligands.

In Nature, enzymatic reactions proceed through exceptionally ordered transition states giving rise to extraordinary levels of stereoselection. In those reactions, the active site of the enzyme plays crucial roles - through one position, it holds the substrate in the proximity to the reaction epicentre that facilitates both the reactivity and stereoselectivity of the chemical process. Inspired by this natural phenomenon, synthetic chemists have designed bifunctional ligands that not only coordinate to a metal centre but also preassociate with an organic substrate, for example aldehyde and ketone, and exerts stereodirecting influence to accelerate the attack of the incoming reacting partner from a particular enantiotopic face. The chief goal of the current review is to give an overview of the recently developed approaches enabled by privileged bio-inspired bifunctional ligands that not only bind to the metal catalyst but also activates carbonyl substrates via organocatalysis, thereby easing in the new bond forming step. As carbonyl α-functionalizations are dominated by enamine and enolate chemistry, the current review primarily focusses on enamine- and enolate-metal catalysis by bifunctional ligands. Thus, developments based on traditional cooperative catalysis occurring through two directly coupled but independent catalytic cycles of an organocatalyst and a metal catalyst are not covered.

Cooperativity between the Substrate and Ligand in Palladium-Catalyzed Allylic Alkylation Using 1-Aryl-1-propynes.

A monoprotected amino acid Bz-Gly-OH assists in the allylic alkylation of a variety of ketones, ß-keto esters, aldehydes, etc., during enamine-palladium catalysis. Density functional theory calculations reveal that Bz-Gly-OH assists in the formation of an enamine that attacks the π-allylpalladium complex via an outer sphere mechanism. The preliminary result points to an asymmetric allylic alkylation under a new mode of bifunctional catalysis.

VacSIM: Learning effective strategies for COVID-19 vaccine distribution using reinforcement learning.

A COVID-19 vaccine is our best bet for mitigating the ongoing onslaught of the pandemic. However, vaccine is also expected to be a limited resource. An optimal allocation strategy, especially in countries with access inequities and temporal separation of hot-spots, might be an effective way of halting the disease spread. We approach this problem by proposing a novel pipeline VacSIM that dovetails Deep Reinforcement Learning models into a Contextual Bandits approach for optimizing the distribution of COVID-19 vaccine. Whereas the Reinforcement Learning models suggest better actions and rewards, Contextual Bandits allow online modifications that may need to be implemented on a day-to-day basis in the real world scenario. We evaluate this framework against a naive allocation approach of distributing vaccine proportional to the incidence of COVID-19 cases in five different States across India (Assam, Delhi, Jharkhand, Maharashtra and Nagaland) and demonstrate up to 9039 potential infections prevented and a significant increase in the efficacy of limiting the spread over a period of 45 days through the VacSIM approach. Our models and the platform are extensible to all states of India and potentially across the globe. We also propose novel evaluation strategies including standard compartmental model-based projections and a causality-preserving evaluation of our model. Since all models carry assumptions that may need to be tested in various contexts, we open source our model VacSIM and contribute a new reinforcement learning environment compatible with OpenAI gym to make it extensible for real-world applications across the globe.

Enhancing the Extent of Enolization for α-C-H Bonds of Aliphatic Carboxylic Acid Equivalents via Ion Pair Catalysis: Application toward α-Chalcogenation.

In general, the α-functionalization of carboxylic acid derivatives requires either a transition metal catalyst or a stoichiometric activating agent/strong base/external additive. A transition metal free α-chalcogenation of aliphatic carboxylic acid equivalents is reported herein via ion pair formation using K3PO4 as a catalyst. Mild conditions, broad scope, scalability of the process, attaining bioactive glucokinase activators, and some synthetic intermediates establish merits of the strategy.

Motivating factors associated with choosing orthodontics for future prospects among newly passed out dental professionals in Maharashtra, India.

BACKGROUND: Choosing postgraduate subject as a future career is always tricky but there are factors associated which persuade the dental undergrads to choose the particular postgraduate course and orthodontics is one of them. Hence, the aim of present study was to determine motivating factors associated with choosing orthodontics for future prospects among newly passed out undergraduate dental professionals. MATERIALS AND METHODS: This was a cross-sectional descriptive questionnaire study. The present study is conducted among the freshly pass out dental professionals who had started their setup. The study was conducted in October-November 2019. The study was conducted among three cities of Maharashtra. Convenient sampling was used to select the samples. A close ended questionnaire was prepared. RESULTS: Majority of study participants {64 (45.39%)} belonged to age group 26-28 years. Females respondents {82 (58.15%)} were more than male study participants. Majority of dental professionals {71 (50.35%)} choose orthodontics dentofacial orthopedics as the specialty for future prospect. Most common reasons {16 (22.57%)} to choose orthodontics for future prospect by majority of respondents was "Can earn more money." Age was significantly (P = 005*) associated with money as reason to choose orthodontic as future prospect. Gender was significantly associated with family pressure (P = 0.01*) and love, interest, and passion for orthodontics (P = 0.01*). CONCLUSION: It was concluded that majority of dental professionals choose orthodontic as their preferred choice. Main reason for choosing orthodontics was monetary benefits followed by the reason that finds orthodontics intellectually and clinically challenging.

Pediatric cervical Hemivertebrae - A Rare Case Presentation in a 3-Year-Old Child.

INTRODUCTION: Hemi vertebrae are very rarely seen at a cervical level which results in kyphotic deformity without coronal tilt. Vertebral formation defects have been the basis of congenital kyphoscoliosis deformity in the pediatric age group. Cervical spine kyphosis more than 10° along with kinking of cord at a single level results in neurodeficits which require urgent management on the lines of decompression, realignment, and bony fusion to prevent recurrence and failure and to achieve superior outcomes. However, in pediatric age group, spine surgeons face a lot challenges with respect to surgical anatomy, body landmarks, and bone anchors. CASE REPORT: A 3-year-old male patient presented to the outpatient department with complain of progressive bilateral upper and lower limb weakness and progressive deformity of the cervical spine which increased in the past 2 months. The patient earlier used to walk with support. However, for 2 months, there was progressive decrease in motor function. The clinical course, radiologic features, pathology, and treatment outcome of the patient were documented. C3 hemivertebrectomy and stabilization from C2 to C4 with fibular strut grafting and anterior cervical plating were done under neuromonitoring guidance. The neurologic symptoms of the patient were markedly improved after surgery. CONCLUSION: We have reported the first case of the management of pediatric cervical spine hemivertebrae with neurodeficit in a 3-year-old child, with anterior hemivertebrectomy, strut grafting, and plating which improved the patient neurologically and functionally.

Direct α-Chalcogenation of Aliphatic Carboxylic Acid Equivalents.

A novel approach to α-chalcogenation of aliphatic carboxylic acids has been developed by means of transforming them as the corresponding benzazoles. The catalyst system, consisting of CuI, DMSO, and a base, operates through a unique mechanism to access a range of practically significant thio- and selenoethers that are otherwise challenging to achieve. The applicative potentials have been exemplified by utilizing the resultant chalcogenated compounds as the precursor for the synthesis of biologically pertinent molecules and synthetic intermediates.

PdII-Catalyzed methoxylation of C(sp3)-H bonds adjacent to benzoxazoles and benzothiazoles.

The Pd(OAc)2/PhI(OAc)2 catalyst system promotes the highly regioselective dehydrogenative methoxylation of a C(sp3)-H bond adjacent to benzoxazole and benzothiazole rings. The title transformation constitutes the first example of a Pd-catalyzed C(sp3)-H activating methoxylation at the proximal-selective α-position with regard to a directing auxiliary and provides expedient access to an important class of azole-decorated methyl ethers (up to 90% isolated yield). The synthetic practicality of the methodology was demonstrated by achieving α-methoxyacetic acids via the elimination of the benzoxazole auxiliaries and by obtaining the precursor of an O-methylated Breslow intermediate.

Chelation-assisted de-aryloxylative amination of 2-aryloxy quinolines: a new synthetic route to a key fragment of a bioactive PRMT5 inhibitor.

A highly regioselective de-aryloxylative amination of O- or N-chelating group-functionalized 2-aryloxy quinolines has been accomplished by means of a copper catalyst. The chelating functional groups of the substrate play a crucial role in directing the C-2-selective amination process, which proceeds through a novel aromatic nucleophilic substitution of the aryloxy group. The methodology provides expedient access to an important class of functionalized 2-aminoquinolines (up to 88% isolated yield) and was successfully applied for the synthesis of a key fragment of an important bioactive PRMT5 inhibitor.

Characterization of human serum immunoglobulin g modified with singlet oxygen.

Reactive oxygen species, as singlet oxygen ((1)O2), is continuously being generated by aerobic organisms, and react actively with biomolecules. At excessive amounts, (1)O2 induces oxidative stress and shows carcinogenic and toxic effects due to oxidation of lipids, proteins and nucleic acids. In our study, immunoglobulin G (IgG) was modified by (1)O2 generated by the ultraviolet (UV) irradiation of methylene blue. The modified IgG was characterized by UV spectroscopy, carbonyl content determination, thermal denaturation and electrophoretic study. Oxidation induced by modification of IgG by (1)O2 also analyzed by scavenging studies. It was found that ultraviolet absorption spectra of modified IgG shows marked hyperchromicity. The carbonyl content was found to be high in modified IgG as compared to native IgG which confirms its oxidation. Thermal denaturation of modified protein sample shows decrease in Tm value by 3 °C and less intensity banding pattern on polyacrylamide gel electrophoresis. The quenching effect of sodium azide provides clue for modification of IgG by methylene blue, as it is known (1)O2 scavenger. Hence, the IgG modified with (1)O2 may be one of the etiological pathogenic factors for rheumatoid arthritis and diabetes.